Abstract
Lipopolysaccharide (LPS), an endotoxin released from the outer membranes of Gram-negative bacteria, triggers cells to synthesize and release inflammatory cytokines that may progress to septic shock in vivo. We found that LPS enhances tetrahydrobiopterin (BH4) biosynthesis by inducing the biosynthetic enzyme GTP cyclohydrolase I (GCH) in vitro in the mouse neuroblastoma cell line N1E-115. Furthermore, we observed that gene expression of GCH in the locus coeruleus (LC) in mice was enhanced by peripheral administration of LPS, resulting in increased concentrations of BH4, and norepinephrine, and its metabolite 4-hydroxy-3-methoxyphenylglycol (MHPG). These results suggest that tyrosine hydroxylase (TH) activity is increased by increased content of BH4 due to enhanced mRNA expression of GCH in the LC resulting in the increase in norepinephrine in the LC during endotoxemia. LPS in blood may act as a stressor to increase norepinephrine biosynthesis in the mouse LC.
| Original language | English |
|---|---|
| Pages (from-to) | 131-136 |
| Number of pages | 6 |
| Journal | Stress |
| Volume | 10 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 01-06-2007 |
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All Science Journal Classification (ASJC) codes
- Physiology
- Neuropsychology and Physiological Psychology
- Endocrine and Autonomic Systems
- Psychiatry and Mental health
- Behavioral Neuroscience
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Effect of peripherally administered lipopolysaccharide (LPS) on GTP cyclohydrolase I, tetrahydrobiopterin and norepinephrine in the locus coeruleus in mice. / Ota, A.; Kaneko, Y. S.; Mori, K.; Nakashima, Akira; Nagatsu, I.; Nagatsu, T.
In: Stress, Vol. 10, No. 2, 01.06.2007, p. 131-136.Research output: Contribution to journal › Review article
TY - JOUR
T1 - Effect of peripherally administered lipopolysaccharide (LPS) on GTP cyclohydrolase I, tetrahydrobiopterin and norepinephrine in the locus coeruleus in mice
AU - Ota, A.
AU - Kaneko, Y. S.
AU - Mori, K.
AU - Nakashima, Akira
AU - Nagatsu, I.
AU - Nagatsu, T.
PY - 2007/6/1
Y1 - 2007/6/1
N2 - Lipopolysaccharide (LPS), an endotoxin released from the outer membranes of Gram-negative bacteria, triggers cells to synthesize and release inflammatory cytokines that may progress to septic shock in vivo. We found that LPS enhances tetrahydrobiopterin (BH4) biosynthesis by inducing the biosynthetic enzyme GTP cyclohydrolase I (GCH) in vitro in the mouse neuroblastoma cell line N1E-115. Furthermore, we observed that gene expression of GCH in the locus coeruleus (LC) in mice was enhanced by peripheral administration of LPS, resulting in increased concentrations of BH4, and norepinephrine, and its metabolite 4-hydroxy-3-methoxyphenylglycol (MHPG). These results suggest that tyrosine hydroxylase (TH) activity is increased by increased content of BH4 due to enhanced mRNA expression of GCH in the LC resulting in the increase in norepinephrine in the LC during endotoxemia. LPS in blood may act as a stressor to increase norepinephrine biosynthesis in the mouse LC.
AB - Lipopolysaccharide (LPS), an endotoxin released from the outer membranes of Gram-negative bacteria, triggers cells to synthesize and release inflammatory cytokines that may progress to septic shock in vivo. We found that LPS enhances tetrahydrobiopterin (BH4) biosynthesis by inducing the biosynthetic enzyme GTP cyclohydrolase I (GCH) in vitro in the mouse neuroblastoma cell line N1E-115. Furthermore, we observed that gene expression of GCH in the locus coeruleus (LC) in mice was enhanced by peripheral administration of LPS, resulting in increased concentrations of BH4, and norepinephrine, and its metabolite 4-hydroxy-3-methoxyphenylglycol (MHPG). These results suggest that tyrosine hydroxylase (TH) activity is increased by increased content of BH4 due to enhanced mRNA expression of GCH in the LC resulting in the increase in norepinephrine in the LC during endotoxemia. LPS in blood may act as a stressor to increase norepinephrine biosynthesis in the mouse LC.
UR - http://www.scopus.com/inward/record.url?scp=34249102925&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249102925&partnerID=8YFLogxK
U2 - 10.1080/10253890701350511
DO - 10.1080/10253890701350511
M3 - Review article
C2 - 17514581
AN - SCOPUS:34249102925
VL - 10
SP - 131
EP - 136
JO - Stress
JF - Stress
SN - 1025-3890
IS - 2
ER -